As reminders…

Alpha–Variant first identified in the UK

Beta–Variant first identified in South Africa

Gamma–Variant first identified in Brazil

Delta–Variant first identified in India

Omicron–Variant first identified in South Africa

Updating the chart above:

Ancestral: B.1.1.529 Omicron

Transmissibility: All the +

Immune Evasiveness: All the +

Vaccine Effectiveness: Check (for hospitalization)

Also as a reminder:

South Sudan Illness:

–Still total silence on this. But, no new deaths being attributed to it in the news. The WHO’s Africa Region weekly report has upgraded the level of malaria in South Sudan to epidemic, including the region where the “mystery illness” was breaking out, so this may be in part or in whole WHO’s conclusion? Not entirely clear. I’ll keep monitoring in case anyone wants to officially solves this mystery in a news report, but will otherwise drop from the weekly update.

QUICKLY WHILE I HAVE YOUR ATTENTION:

–The Colorado wild fires last week that torched so many homes forced the evacuation of one our readers. They and their family have fortunately come through, home and hearth unscathed. Many of their neighbors and friends were not as lucky. Per the reader, one of the best places to donate is here.

Coronavirus Update:

–Fair warning–this will be a long update, mostly because we are going “Plandemic” deep on a popular interview from this past week. So get your tea or coffee ready and set aside some time.

–The biggest, but under-reported story of the week is a team from Baylor has developed and successfully tested a new COVID vaccine, and India just granted emergency use approval for it.

The big kicker? They are providing it patent free (although Baylor will get a small fee) and partnering with generic manufacturers around the world to make it affordable for developing nations especially. In Phase 3 clinical testing in India, by report (the data is not published yet) shows slightly better efficacy than the AstraZeneca vaccine it was put up against in terms of preventing symptomatic disease. It’s also worth mentioning the Phase 3 studies were done by one of the generic manufacturers in India, who do expect to make at least a little money on the vaccine, as is pointed out by a virologist interviewed in the linked Washington Post article.

That said, and equally of note, this vaccine project (Corbevax) received hardly any government support via Operation Warp Speed. Instead, the $7 million dollar cost was covered by private donors, including $1 million from Tito’s Vodka alone.

Corbevax is a more traditional vaccine, which injects just the spike protein. So this is not mRNA making the spike protein, but the fully formed spike protein itself. This is also not a weakened or inactivated full copy of the virus, like some of the Chinese vaccines.  Instead, ONLY spike protein is used after being manufactured in a lab, and then combined with an adjuvant to get macrophages, the clean up crew of the body, to eat it.  They then show the pieces of what they eat to the immune system, in case they have eaten parts of bacteria or viruses that the immune system needs to know about. 

This is pretty much how the Hep B vaccine works too, so there is precedent for this vaccination mechanism. 

All that said, they need to publish the Phase 3 data before they are going to get a look for use in the developed world, at least. If the publications match the press releases, and the data looks good, will be interesting…to say the least…to see if and the speed at which it is adopted by FDA and similar Western authorities, most of which will probably insist on another Phase 3 in their patient populations before approval. Before you get too conspiratorial, this is quite common. Since an India only study may not be representative of the different demographics and patient populations in Europe or Africa or the US, it’s common to do either a multi-country international study for the registration intent Phase 3 (to cover that upfront) or do Phase 3s in each region separately. Japan, for example, is famous for insisting on a separate trial in Japan before they will even look at your data. And with just $7 million in the bank, these guys were ballin’ on a budget, and a multinational Phase 3 out of the gate was just beyond their budget. 

Regardless, if the clinical data holds, this will be a huge benefit to the developing world, and I am sure makes Pfizer and Moderna and all the other current vaccine makers at least a little worried about upcoming earnings calls. A lot worried if the data looks good and they open registration intent Phase 3s in the developed world as well to compete with the existing vaccines.

From a more sociological standpoint, I am also now morbidly curious to see if the vaccine safety questioners and anti-vaxxers will have concerns about this vaccination method too. A lot of the criticisms start with a “for profit” and “follow the money” assumption, and then look for at least plausible safety risks that were steam rolled “following the money.”  Particularly the vocal set that alleges “spike protein itself is a toxin!” Their take on this vaccine’s safety data, absent -any- money to follow for conspiracy to conceal safety signals, will be interesting.

–As a complete aside, apropos of nearly nothing, to release a massively useful medicine patent free and at the cheapest possible price to get to as many patients, desperately waiting, as possible as fast as possible is the dream.  There are some shots on goal at cancer I am really eager to take, but have been so busy in COVID land that I increasingly despair that our oncology unit here will take them.  I have been starting to look into NFTs and DAOs (seriously) since Naval Ravikant and Tim Ferriss were talking about them as new ways to raise funds for projects and companies.  In fact, in ~November of last year, Ferriss was trying to convert his non-profit to this DAO-like model because it would make it easier to fund certain charitable causes without having to re-draw charters and the like.  I still worry about governance and law for these types of organizations, but if you can get a non profit organized and funded by tokenizing it on a blockchain, then that could be viable as a way to hold a digital bake sale for cancer research.  And that would be worth looking into if log jams here don’t clear—cancer isn’t exactly waiting.  Anyways, long way of saying if you can explain to me like I’m 6 how to do something like funding a research project via NFT or FT, and run it as a DAO—or know someone who can and can put me in touch, please reach out!

–Otherwise, around the horn, omicron is rampant. So rampant that places ranging from the UK to Florida are asking those NOT symptomatic to NOT get tested to increase testing availability. I have argued before that PCR tests, in particular, are best reserved for symptomatic patients, so nothing more to add here.

So while new cases are exploding everywhere due to the high contagiousness of omicron, there is now consensus that omicron is, indeed, more mild than previous variants. I know that comes as no surprise to anyone reading this update, but I assure you, based solely on the headlines I had to “special edition” the day after Thanksgiving, as well as several weeks now of “just because it hasn’t been as bad in South Africa doesn’t mean it won’t be bad here,” that comes as a big surprise to some.

For those keeping score at home, South Africa was timely with the identification, transparent with the warning, and timely and transparent with the relevant clinical data to provide appropriate context to the variant of concern they identified. They did everything right that China was doing wrong in late 2019-early 2020.

Now the trend to watch is timing of the new case drop in the UK. They are the western nation most heavily hit early by omicron, and their peak should give indication to the timing of the US peak. Bear in mind, there will be some wiggle, as omicron has generally been sweeping East to West coast, really only getting started in Cali this week.

China is also struggling with a growing outbreak, likely of omicron, and it’s “No COVID policy” of widespread shutdowns and lockdowns for case numbers most other countries no longer blink at is an own goal that may reverberate around the world again this year. We’ll get to that towards the end.

–Big story that WAS covered a lot this week was Joe Rogan’s interview with Dr. Robert Malone. You can find this on the JRE on Spotify again (you will likely need a premium subscription to listen). It’s JRE 1757. Otherwise, you may have to Google and hope Spotify’s guys have not swatted a copyright violation yet so the full video is still up on somebody’s site or channel somewhere. I suspect that, more than anything, copyright violation claimed by Spotify is responsible for the full interview being booted off YouTube earlier this week, where it was posted by non-official JRE accounts. Not necessarily anything nefarious by YouTube. That said, there are no clips from the interview on the JRE YouTube channel, which is…unusual. Dr. Malone was permanently kicked off Twitter right before this interview. No explanation was given, but as Dr. Malone concedes, Twitter does not typically identify the tweet they feel violated their ToS. Later headlines suggest that this suspension was for vaccine misinformation; Dr. Malone does indicate at the end of the podcast with Joe that he has been contacted by lawyers to sue Twitter for violation of free speech.

Dr. Malone is an MD, specifically a pathologist by training. He describes himself more as a virologist, and has been heavily involved in vaccine development and response to other viral outbreaks over the years. He is well published and knows many of the famous faces of COVID on the medical side. For example, he knows Dr. Fauci personally from previous work as a study section chair or member for NIAID grants (Dr. Fauci is the head of NIAID). Dr. Malone has also led infectious disease relevant Department of Defense study sections, including as chairman. All of that is research-ese for saying he was on, or chairing, committees for the NIAID and DoD that were determining which vaccine or infectious disease research proposals would get funding from grant money available from those organizations. Goes without saying they form those committees of recognized experts in the area involved to (hopefully) direct that public grant money to the most worthy projects. He is listed as a co-inventor of several of the patents that underlie delivery of, and therapeutic use of, mRNA.

In one of the turns of language that probably bothers only me, Dr. Malone did NOT “invent mRNA,” which is one of the ways his co-inventorship on these patents is horribly tortured in the media reports about him. mRNA has been around for hundreds of millions of years–it’s how your ribosomes “read” the message sent to them from DNA, as we have covered before. Dr. Malone DID patent ways to modify or custom design mRNA and deliver it to cells to use mRNA therapeutically, and yes, these patents underlie how the mRNA vaccines are functioning. That is fair. As far as I am aware, he is truthful in saying he is not profiting from any kind of royalty on these patents, likely because the usual deal is that these are signed over to the institution, and then licensed out by the university or company (similar to Baylor getting a fee, but not the Texas Children’s individuals on the COVID vaccine above). There are sometimes provisions for an individual cut, but not always. Neither here nor there though.

So the other way Dr. Malone’s patents get mangled is ham fisted attempts to discredit him based on claims about these patents. You’ll see articles that say “virologist who claims to have invented mRNA”, and then explain that these are not the patents specific to the mRNA vaccines and thus he must be a dirty, dirty liar. To the best of my knowledge (which is pretty much this podcast), Dr. Malone has not and does not claim to have invented the mRNA vaccines for COVID. He did do foundational work on how to use and deliver mRNA as a general therapeutic strategy, which the vaccines use, and can speak to that.

So in overall fairness to Dr. Malone, he’s a pretty credentialed dude with plenty of regulatory experience and vaccine development experience.

And of course, magnetically charismatic and spectacularly good looking like all pathologists are. : )

So I am going to give my take on this interview in approximate order of topics discussed. I may move a few things as a bit as I am basically expanding on my notes here.

Right off the bat, we go from introducing Dr. Malone and his background to Dr. Malone’s “controversial take” on the vaccines for COVID (you can find a bazillion articles on Google using “controversial take” about this all over them).

Alan Watts had another good soundbite gem once, saying how paradoxical it could be to examine something and how it functions at one level, or magnification, while at a different magnification it appeared to be something entirely different, and function entirely differently. For example, these are both pictures of the same thing:

The top image just happens to be a scanning electron microscope, while the other was taken with a regular camera. While they are the same thing–pictures of a bee–the resolution is so different at the different magnifications as to make the top look very different from the bottom. If I sent these through “Google Image”, and asked an AI to tell me if they were the same object looking at nothing else but the picture, most of the AIs would fail. The bottom image would not return anything that looked like the top.

Similarly, things that work on one level of organization and size don’t necessarily work the same on other, more or less complex levels of organization.

What should not be, but is, controversial is that as a public health measure, vaccination has failed to prevent aggregate spread of SARS-CoV-2, and/or the development of new pandemic waves of SARS-CoV-2, even in countries with vaccination rates at what we would have expected to generate herd immunity. No country thus far has been spared delta and omicron waves based solely on its vaccination numbers. Small island nations, for example, have been a little more resilient, but ability to, and enforcement of, hard curbs on entry and exit have been more explanatory. And even some of them, like New Zealand, have eventually lost the fight to highly contagious strains like Delta.

We are speaking here purely of new infections, with or without symptoms, and including merely screening PCR positives that are otherwise asymptomatic. Vaccination has not stopped those.

That public health level outcome is surprising, and disappointing. In fairness, there should also be enough vaccination and natural immunity from prior infection that herd immunity should have been reached in many countries. The US, for example, should be there based on studies released by CDC estimating that well into the 80%s of the population had vaccine or natural immunity. This should have been more resistant to the new case numbers, official and unofficial, of omicron, for example. This has not been the case.

Hell, just this week a station in Antarctica was hit by a COVID outbreak in more than half of the crew. Despite being as remote as possible, despite testing, and despite all of them being vaccinated (many with boosters). Although being pushed as the solution, with varying degrees of legal compulsion towards that solution, vaccines have been an imperfect solution…

…at the level of public health. At least for stopping new cases from happening.

The public health success of the vaccines comes from its effect at a different level.

Vaccines, -and natural immunity- reduce the individual risk of symptomatic disease and most especially preventing severe, hospitalizing COVID on subsequent exposure to SARS-CoV-2. None of the antarctic crew in the outbreak have been hospitalized, for example.

The individual success at reducing hospitalization or worse from SARS-CoV-2, as we have stressed before, is the most important pandemic success metric–as the main pandemic risk is “bed’s taken” and overall mortality increases. SARS-CoV-2 is a direct threat only to well known high risk factor patients–and even then, is nowhere close to the mortality of, say, Ebola.

Similar to masks, the vaccine clearly reduces your individual risk. At the public health level, well, real world results depend mostly on the metric you are looking at. If you want vaccines to stop new case numbers, which appears to be the main driver of political reaction to the pandemic at this point, vaccines have been imperfect. If your public health goal is reducing hospitalization (again, the main pandemic threat of SARS-CoV-2 from a medical standpoint, and, I would argue increasingly, social standpoint), vaccines have been doing well.

So the interesting paradox, and “controversy”, is that the vaccines, at one closely watched public health level, have NOT stopped new positive tests and mildly symptomatic cases of COVID, or concern about case numbers provoking various forms of social restrictions. At the individual level, and a different focus of public health, the vaccines have worked quite well, reducing the chances of severe COVID by ~10 fold, and thus reducing the hospitalization rate. That in turn achieves the goal of reducing the “bed’s taken” resource burden on hospitals.

Before you @ me about the news stories of hospitals full to the gills of COVID patients right now, requiring military help, with supply shortages, and yes, I have even heard of a car accident victim here in Indiana this week who could not get the right level of care because there were no available beds (and ultimately died of injuries)… that is a function of sheer number of positive cases, burnout and staffing pressures in the hospitals, and yes, even the individual vaccination effect, as the numbers of patients in the hospital with severe COVID remain disproportionately non-vaccinated patients. That is also impacted by availability and use of early COVID treatments to keep patients out of the hospital (we’ll get back to this point, as Dr. Malone will discuss it a bit too).

It’s also impacted by omicron itself being more contagious, as hospital staff are popping positive too, with the same quarantine commitments that have had patients complain to me about the “inconvenience” of COVID being their worst part of the otherwise mildly symptomatic experience. Positive results in the hospital staff are driving these stories too.

So many of these “controversies” are true, even simultaneously true–just at different levels of magnification in a very complex interaction.

Continuing on, Dr. Malone has been critical of the expedited process of testing these vaccines, and has some strong comments on them. He is correct in saying, as we did, that Phase 3 studies will catch common severe adverse events; they may not catch less common, but severe events. For example, the myocarditis risk from the mRNA vaccines is rare enough that one would not expect to see it on a Phase 3 study unless that study got really “lucky” to enroll a patient who would wind up developing it.

So Dr. Malone has some comments on these risks, mostly from an ethical standpoint. Are we informed enough? Do we know enough about these risks for patients and doctors to make truly informed decisions? Do we have information for vaccine mandates, population wide, to be bioethically justifiable–realizing that the standard there must be higher, considering the broad differences when talking about the people who make up just a single nation.

Bit of a spoiler here, but Dr. Malone does -not- believe that standard has been reached.

Also a bit of a spoiler, Dr. Malone has received a full vaccination series himself–two doses–and caught COVID twice. Once was early, since he was at one of the scientific conferences that was a superspreader event at the beginning of the pandemic. The other was apparently breakthrough. He did concede that the main reason he got the vaccine was because he knew it would be required for international travel. Also worth mentioning he will go on to state that vaccination of the previously infected, and thus naturally immune, may be placing them at higher risk of adverse events from the vaccine. Even though he himself got vaccinated after recovering from COVID, and getting some degree of natural immunity.

I do agree that the individual level is where risks versus benefits of vaccination should be balanced. For those over 60, for example, or with known high risk conditions for severe COVID, such as obesity, diabetes, pregnancy etc (which is an unfortunately high percentage of the population), the benefits of vaccination exceed the risks. For these same groups, the benefits of a booster likely exceed the risks as well. For those who are younger and are not high risk, well, frankly that risk/benefit line gets more blurred.

Let’s take, for argument’s sake, a 32 year old male in otherwise good health and run them through the COVID mortality risk calculator here. With slight differences for race and zip code, the chance of death from COVID if they do not get vaccinated is ~2.5 per million. We’ll ball park it as x5 for chance of hospitalization, so 10 in a million. With a vaccine, the chance of dying or hospitalization falls by ~10. There are only about 10 million, give or take, 32 year old males in the US. So their odds break down as with vaccine, the chance they would die of COVID is the chance that they would be the only guy with their age and history in the US to die that way. Not very likely. Without the vaccine, they might be one of only a handful. The vast, vast majority of people their age and medical history will not have a problem with COVID.

“Well, they will reduce the risks of spreading it to others if they vaccinate! It’s responsible to do anyways,” is the one argument. Well, let’s remember, there are risks of side effects from the vaccine too. And they are lower, but not enormously so, than the chance of an individual bad outcome if they don’t vaccinate.

As for risks of spreading, well, let’s remember, vaccination is not a panacea for preventing spread of COVID based on both delta AND omicron waves. Just look at Israel, with one of the highest vaccination and booster rates in the world:

Dr. Malone will even mention the difference in Palestine and Israel in terms of new COVID cases and severity versus vaccination rates. This leads, as it should, to discussion of confounding variables like different average age levels and other health indicators between the two countries. Same for the malaria belt in Africa. Differences in case numbers and severe cases may also reflect disparities in testing availability too, as another confounder.

Regardless, the best medical reason (setting aside mandates etc.) for vaccination is the 10 fold drop in severe COVID risk to you, individually, especially if you have not had COVID before. And the best public health reason for the vaccination is because it drops your risk of taking up one of my hospital beds by 10-fold, I have fewer COVID patients soaking up beds.

I can promise you, without the vaccines, delta would have caved in multiple US health care systems by taking up way too much bed space when at its peak. Even though comparatively mild, omicron would be making a run at it locally given the rampant it has been these last couple weeks.

Dr. Malone argues, as we have, that those with natural immunity may not benefit as much, if at all, from vaccination. He is a little more critical of the CDC’s data on natural immunity versus vaccine immunity, and goes into some limitations of their publication, and how it compares to the two much larger Israeli studies we have already discussed. Dr. Malone believes those with natural immunity who get subsequently vaccinated are, in fact, higher risk for vaccine side effects, although I personally believe that has more to do with timing of vaccination following recovery. As we have mentioned, if you go into an immune system that is still loaded for bear from recent COVID recovery with the big doses of spike protein the mRNA vaccine will cause to be generated in your cells, you’ll get a very angry immune system that is a little more likely to cytokine storm or go Ah-nold. And that over-exuberant immune response is the source of most of the side effects. Every natural immunity person I know or have heard of who had a bad vaccine experience got vaccinated within a month of recovering from COVID.

It is worth mentioning again that Dr. Malone is personally one of those who naturally recovered and got vaccinated, and clearly appears to correlate his new onset hypertension to the vaccine he received.

There is no mention in the podcast, but (hopefully I have conveyed this clearly) my personal belief is that more routine use of antibody titers can help select who needs a vaccine/booster and who likely has sufficient immunity already and can delay vaccination/booster. Especially if health authorities are going to continue to use those same titers to argue “waning immunity” and “see–a booster restores it!” These would be more useful than a blanket vaccine mandate, and better inform risk/benefit decision making to the individual patient-healthcare provider relationship. There should be far more routine use of the available COVID risk calculators as well to help inform some of the individual risk benefit decisions.

Instead, we went mandates.

Now, Dr. Malone gets a little conspiranoia and “follow the money” about that. Again, while acknowledging that “follow the incentives” can explain a lot of otherwise odd decisions and behavior, I hesitate to attribute to malice that which is best explained by laziness/stupidity.

Again, it’s just way, way easier for the government to mandate vaccines for everyone and then count shots out rather than the messy data of tracking everyone’s COVID diagnostic tests and antibody titers, and making guidelines that recognize the gray areas of individuals who have good medical reasons (i.e history of blood clots) to be vaccine hesitant. That the lazy route may also have coincided with financial incentives for some who may have been involved in the decision making was probably just seen as happy coincidence by them. And I have no doubt that those instituting mandates actually genuinely believe in their effectiveness, and they are helping many others do the best thing for their individual risks. But they are going to force some of the edge cases, like those with autoimmune disorders or pre-existing conditions, or even the rare allergies to some of the vaccine components, or those who recently got over COVID but now have to meet an arbitrary deadline from their employer, into tough social cost judgment versus very real medical risk to them in complying with a vaccine mandate.

And yes, this is very relevant as this week, the government approved boosters for the 12+ age cohort.

On a similar vein, though, Dr Malone’s comments on the -regulatory- and government decisions around ivermectin and hydroxychloroquine are worth listening to.  He knows the players well, and was in a position to be better informed on them than me. I will say there are entire countries that believe in ivermectin and use it front line for acute COVID (before it reaches the hospital). Again, my personal take is that the best Phase 3 study of it out there only showed a trend in favor of ivermectin, and would need more patients to confirm any benefit of ivermectin in this setting. Ivermectin does indeed have a fantastic safety profile. I understand why some physicians around the world are still using it for COVID, following that trend. It might help–but I think there is, at best, “anecdotal plus” and a trend that did not reach statistical significant as evidence to that.

Continuing to roughly follow the interview with Dr. Malone, I agree that total death counts are iffy, and why I have not stressed them. They are iffy precisely because of the “dying with” vs “dying of” COVID, and how messy death certificates and cause of death determination can be. A lot of that is judgement call.

That being said, I am sure there have been a lot of deaths with people legitimately dying of COVID. Have there been enough of those definitive deaths due to COVID to say 500K excess deaths would have been prevented with early treatment–which is what the modeling studies Dr Malone was so adamant about at the beginning of the podcast claim, I’m not sure.  If you’re not certain about death counts of COVID, and are going conspiranoia about hospital financial incentives to call a death a COVID death, how are you possible that sure that 500K of those deaths that may not be COVID at all were preventable by early COVID treatment?

Regarding that bit of conspiranoia, hospitals getting paid bounties to call COVID has been discussed before in this update. What they are talking about is an adjustment because intensive care of COVID patients was running hospitals into the red early in the pandemic–it was not getting reimbursed to them. Again, recall many hospitals were having serious financial difficulty very early on in the pandemic. The hyperbole-to-make-a-point case Dr. Malone makes of a trauma death being classified as COVID for a death bounty is frankly implausible, and gilds the lily a bit too much as an example. You can access death certificate records and some conspiracy nut should have already run those records and found examples that egregious of a clearly non-COVID death being called COVID to claim a “death bounty” (I’m not sure exists–if someone can find what he’s talking about, please send) for the hospital. To me, the lack of a consparanoia blog post with case after case of gun shot victims who happened to test positive for COVID due to hospital admission screening policy getting called a “COVID death” when they didn’t make it is a curious incident of a dog not barking in the night if this were really widespread. It’s telling that when Joe pushes back on the implausibility of this that Dr. Malone states explicitly he is not certain how common it is, and what or if the exact payment is, as he is not a hospital administrator or hospitalist.

Further, if you are gaming CMS by upcoding, they will absolutely come after you. The minutiae of that is why medical coding exists as a well paid job. A gun shot wound (or similar egregious non-COVID caused death) that then claimed a COVID upcode seems -highly- likely to get flagged by Medicare and/or insurance for possible error or fraud—what Medicare would call a “medically unlikely edit”. Each instance of healthcare fraud, whether coding a bill too high -or- too low, was a 40K fine –for each– when I was in residency. And the burden of proof was largely on you if Medicare accused you of coding malfeasance. If we are following the money and incentives, well, those are the reasons to NOT be falsely claiming COVID “death bounties” if you are a hospitalist or hospital administrator.

On the flip side, am I confident enough in the way death certificates get filled out, and data collected and tabulated, to say that total deaths due to COVID in the US are 800,000 to a million in the US (and counting)–with the high confidence and precision those numbers are thrown out there by the media? 

No. 

There are undoubtedly a number of “with” not “of” in those tallies and we have covered how messy that data is at the local level in some places, even in the US.  For example, even Dr. Fauci recently conceded that the vast majority of kids coming into hospitals during this wave have been admitted for something else, with COVID on incidentally found via a positive screening test. So “with” not “of”. Even saw an article Thursday saying omicron is “different” in the hospitals because most patients are being admitted for something else, but popping the hospital’s mandatory COVID screening positive. That “with” not “of” quandary will absolutely extend to death certificates and calculations.

Overall, I think -somewhere- in the solid 6 figures dying -of- COVID in the US seems a reasonable estimate though.

It’s also worth mentioning and pondering that the life insurance companies are now griping about a 3-sigma increase in the number of deaths among the 18-64 set, over and above what they would have expected prior to the pandemic. Now, when asked, they clarified that COVID alone does not explain it. People, as mentioned, are coming to the hospital generally sicker of a lot of chronic things that were either not caught during COVID shutdowns or not able to followed as clinics were closed for lockdowns or diverted to COVID care. Throw addiction deaths on those too, which rose sharply, and that’s the very human cost of some of the more draconian responses to COVID. Yes, those are working age adults in that cohort, and yes, that is going some distance to some of the labor shortages around you. The lost productivity, training and skills in those excess deaths among the working aged will also subtly reverberate for years to come, until the kids age into those jobs and roles.

That insurance data point happens to cut against both arguments here. Early treatment, for COVID, of those 18-64 dying of non-COVID reasons would not have saved an extra 500K of them, as the model Dr. Malone is touting suggests. That the increase in deaths in the actuarial data is not directly attributable to COVID also argues that the 800K-1 million US deaths alone stat being waved around is most likely an overestimate.

At the same time, it also illustrates the pandemic threat of COVID. It’s not COVID specific mortality–it’s all cause mortality, either from bed’s taken or the psychosocial impact of that increase in all cause mortality and responses to the pandemic.

So Joe and Dr. Malone move on to discuss Uttar Pradesh, the most populous region of India (about 2/3rds the population of the entire United States for comparison), which “crushed COVID” during the delta wave and at the time of the podcast had minimal disease activity. This part gets very conspiranoia, as Uttar Pradesh’s response to COVID included a widely distributed early treatment package that was given to every acute positive case at the height of the delta wave. Dr. Malone attributes success in COVID management in this province to this systematized early treatment regimen, and whatever was in that packet. We go to borderline conspiracy land when Dr. Malone argues that the contents of Uttar Pradesh’s successful early treatment packages are being suppressed by the Indian government after a meeting with Joe Biden–which may or may not have involved discussion of the early treatment packages.  Dr Malone is careful to say only that this meeting happened, he doesn’t know what was said, but the Indian government then made contents of these packages secret afterwards.  “Make your own conclusions,” is his direct quote.

Really a quotation of -any- of your favorite conspiracy documentaries that have a major insinuation, but no access to either a smoking gun or data that would definitively refute the claim. Always “make your own conclusions.”

The idea that the US President somehow conspired with the President of India to cut some sort of back room deal to suppress an effective early treatment regimen to a pandemic that has globally made life miserable is an extraordinary claim, which would require extraordinary proof. I am as incredulous as Joe Rogan was in the podcast that the contents of that package have -not- leaked, given the medical need and sheer number of people in India who have to know what is in them.  Again, there are 200 million people in Uttar Pradesh. Someone would have spilled by now if that regimen was that effective.

Regardless, for all the claims that Uttar Pradesh has “crushed COVID” and has basically zero disease activity, well, omicron had not made its way there yet when Dr. Malone was on the JRE. This week, omicron has been arriving and Uttar Pradesh announced new restrictions for social distancing on Wednesday as their cases have essentially doubled every day since the weekend into the thousands, with no near term end in sight to the climb.

Dr Malone also gets out over his skis calling the PCR non-specific around here (really, in the “corrupt hospitals inflating COVID cases for a bounty” section) and a bit later in the podcast.  Most of the PCR assays out there are highly specific and why the rapid respiratory pathogen multiplex tests work, where COVID is tested alongside multiple other common causes of similar symptoms (including flu), and the test tells you which agent was positive, and thus likely behind the symptoms. A good example of one of these multiplex assays is here.  It’s worth noting that linked example is a different PCR assay than the original CDC form, and different from some of the other PCR assays listed it was tested against in that paper. That’s a way of saying again not every PCR is created the same, so blanket calling them all non-specific especially at a particular Ct number is way to tell me without telling me that you don’t do a whole lot of diagnostic PCR. Regardless, whatever assay you choose to detect SARS-CoV-2, as a clinical lab offering it as a clinical test, you are required to test it in your lab to prove specificity before running it on patient samples. 

As we covered before, the problem is not the analytic sensitivity and specificity—it’s the use of PCR as a -screening method- in the asymptomatic, risking false clinical positive by detecting inactive virus in a patient who was never going to spread it. Which has led to the CDC’s recommendation (accurate as of the day I am writing this–I know, it changes a lot this week) that a PCR test after symptoms have passed is no longer required to exit quarantine.

We next get into a discussion on theoretical risks to women’s reproductive health from the vaccine. Dr. Malone mentions data from Pfizer that was submitted as part of their approval package in Japan, and states that it worried him and some others who have done a lot of vaccine development work. The particular study was looking at the distribution in rats (not humans) of the lipoprotein particles that carry the mRNA in the mRNA vaccines. Of note, they did NOT have the mRNA loaded for this study.

Also very important, but not mentioned by Dr. Malone, is that the dose of these lipoproteins injected into these rats was 18-35 times higher than the dose in the vaccine, once adjusted for the weight of the rats. So there is a LOT more of these lipoparticles going into the rat than into you.

Dr. Malone does correctly state that the great majority of the lipoparticles stay at the injection site. But, ominously, “not all of them do, as we first thought.” He highlights that a number of the lipoparticles are detected in the ovaries, and suggests that if they were carrying the spike protein mRNA (as they are in humans who receive the vaccine), ovarian cells can be “infected” by the mRNA and produce spike protein in the ovary. Which may be damaging to fertility. This section gets a little confusing because Dr. Malone really does sound like he is claiming that spike protein is in the vaccine–it’s not, the vaccine just causes it to be made. Regardless, he highlights that the protein may have damaging effects in its own right, and why this ovarian concentration is theoretically concerning. He highlights a Jewish community that recommended against its female members getting vaccinated because they noticed some complaints of menstrual irregularities after vaccination in some members. That may be a different problem than fertility issues.

Regardless, there are some hurdles in the way of this hypothesis. First, set aside for a moment that you massively overdosed these rats, and the amount that makes it to human ovaries is likely much less than what was seen in this study. Set that aside. When you look at the distribution of the lipoparticles in this data, again, most of the dose stays at the injection site. Of the rest, it largely follows the distribution of blood. Dr. Malone states that it is “surprisingly” concentrated in the bone marrow. That’s not a surprise at all–bone marrow is very vascular. In fact, the next highest concentration is in plasma, or basically still circulating in the blood, probably having not successfully “infected” a cell at all yet. After that, it’s liver, brain, spleen, adrenal, kidneys. Basically, there is a LOT of overlap with the expected distribution of blood flow to the various organs. The ovaries have a pretty decent blood flow from the ovarian artery. Not a surprise that the collection of lipoproteins looks pretty close to the blood volume that gets there. So it’s hard to argue it is concentrating excessively in the ovaries–but sure, the lipoproteins make it to blood vessels there. The study is not designed to know if the lipoproteins detected are free flowing in the ovarian blood vessels or actually in ovarian cells.

Secondly, most importantly, if spike protein expression status post vaccination was happening in the ovaries AND affecting fertility, we should see it by now. Millions upon millions of doses are out. The idea that spike protein may impact the ovaries, eggs, and fertility was tested for explicitly in small, but focused studies on in vitro fertilization patients. These patients arguably should be most at risk for fertility issues with vaccination, since they were struggling already. There is a good one here that set out to directly refute the former Pfizer respiratory VP (from like 10 years ago) who first made claims about overlap with syncytin-1 in the ovary and the mRNA vaccines, with possible infertility issues (we covered that nonsense awhile ago in an update too). But the best is one that looked at IVF success rates in women with the vaccine, with COVID infection and with no known COVID exposure and found no difference in IVF success rates among the three groups. If Dr. Malone’s hypothesis is correct, IVF results should have been worse in the vaccinated group, possibly the prior infection group too, versus no known exposure. They were not. Strike against the hypothesis here.

But the best argument against the “impaired fertility by vaccination” hypothesis, again, is the millions of doses out in the real world already. If there were common, even merely uncommon, hell, even somewhat rare infertility issues after mRNA vaccination, I would expect that we would have heard more about them by now. Or that IVF clinics are just getting blitzed with new patients, or odd patients with none of the usual suspects that would cause one to need IVF referral. To the best of my knowledge, that has not happened to the IVF guys. I may just not be aware of it though, so if someone else has heard differently, please reach out. Otherwise, this dog just ain’t barking.

This segues into a discussion on autoantibodies from SARS-CoV-2 infection that may also be generated by the vaccine in some patients, and may explain the symptoms of “long COVID” and some of the vaccine adverse events. These autoantibodies were recently published upon, and this seems pathologically quite plausible. You can find a good article on it here.

They go from there to discuss reduced T-cell responses in aging, often as memory T-cells begin to “age out”. I don’t think this was addressed directly, but it is tempting to speculate that this is also part of why COVID may be more likely to be severe the older you are. Especially since I have been tempted to speculate early and often that T-cell response is likely the key determinant of if you get severe COVID or not in the acute infection, and that basically, if your T-cells get on the job fast, you control the virus well. If your immune system chooses poorly and goes B-cell heavy after the virus is already inside many of your cells, that response is less effective, and the immune system freaks out, goes into hyperdrive, and the Ah-nold reaction that causes severe COVID results. Poor T-cell activation in the elderly may play a key role in that, so good on Dr. Malone here.

And oh look–new research that suggests that memory T-cells from previous infection or vaccination are responding to omicron, and that T-cell response may be helping keeping cases, especially breakthrough cases, super mild! Agrees with me, so obviously genius research that should be in strong consideration for the Nobel Prize–my confirmation bias be damned : )

Dr. Malone then makes what are frankly anecdotal claims about new and more serious, aggressive forms of cancer showing up after vaccination, mostly because continually reintroducing an antigen can cause T-cells to basically go into torpor. For example, this is how we desensitize from antigens. If you are allergic to ragweed, it’s because your immune system sees ragweed is this dangerous foreign invader that must be KILLED WITH FIRE. Since ragweed is seasonally quite common, this overreaction can be a serious allergy problem. So to stop that, we just introduce more ragweed more often, until your immune system goes, okay, this is foreign, but I don’t need nuclear weapons for it. Your immune system, including the T-cells responding to ragweed, is now chill in the presence of ragweed, and allergy problem solved or severely reduced.

So one of the claims Dr. Malone makes here is that the vaccine causes a small window of increased infection susceptibility as the T-cells are a little too busy dealing with COVID, and that may extend to T-cells that ordinarily hunt down and execute precancerous cells in your body, which go into “chill” mode as the others are fighting off a big dose of spike protein from the vaccine.

I frankly cannot find much for or against this right now. It’s a hypothesis based on anecdote right now; he’s got a guy claiming he’s seeing more cancers, but that could just be random chance and that guy’s practice is just going through an unlucky stretch. On a theoretical basis, the mRNA for the spike protein is there and gone. The immune response window to the vaccine is measured in days. This is an extraordinary claim to me, and I look forward to extraordinary proof of it.

The other argument that is teased out here is that repeated jabs, particularly TOO frequently, of the same antigen may, just like allergy desensitization, cause the immune system to think SARS-CoV-2 is common and benign like ragweed, and start ignoring it. If that is the case, we would expect boosters, particularly repeat boosters, to be paradoxically more susceptible to COVID.

In fairness, there is data this week from over 10,000 patients in Denmark followed for omicron. The highest risk of infection was in patients who had received a booster, followed by those who were vaccinated, followed by the unvaccinated.

–BUT–

Don’t overinterpret that study. There are -significant- confounding variables there. For example, the unvaccinated include patients who have natural immunity, and we know that is more resistant to re-infection already, and may be more so to omicron as well. More importantly, those receiving boosters are a combination of those likely required to get boosters to go work jobs and do things that put them around people and thus higher risk of actually catching COVID and high risk patients more likely to develop COVID if exposed, hence, they were a booster priority.

So not sure it proves anything any which way, other than omicron is getting through both vaccine and boosters to some extent. And probably some natural immunity as well. Just with very mild breakthrough symptoms typically.

The conversation then stays with the current COVID booster approach, criticizing it as equivalent to “taking the same flu vaccine from two seasons ago and hoping for protection this year.” Especially as vaccine resistant variants have emerged.

That’s actually a pretty fair claim to make, given the breakthrough rate even on those relatively recent booster shots. I mean, we mentioned just last week that the UK was already concerned that the boosters were only effective for ~10 weeks. Then you have the Danish study we just mentioned. I also have anecdotal reason to believe it may be a month or less of booster protection against symptomatic infection by omicron. Regardless, those breakthroughs, when the occur, have typically been mild cold symptoms with most patients complaining of the inconvenience of testing COVID positive, that is here and gone in a few days. Protection against hospitalization, which it the more critical metric, remains quite high.

Certainly, taken together, and as Dr. Malone stresses, it highlights the importance of effective and widely available acute phase treatment of COVID, when the virus is first getting started, as a way to further reduce hospitalization or worse outcomes, and stress on the health care system from “bed’s taken.”

We then get a little talk on antibody-dependent enhancement, or ADE. The argument here (which we have covered before as well) is that the antibodies may accidentally help SARS-CoV-2 get into cells and make infection worse. You can read up on it at the link, because this is the same argument another physician on a viral tear made. The best refutation of ADE with the vaccine is we would expect COVID to be worse in vaccinated patients. With billions of shots out, and multiple large studies across the world looking at outcomes following vaccination, the vaccine is instead ~10x more likely to keep you OUT of the hospital. Not quite as good as natural immunity from prior infection, but that is still definitely NOT consistent with ADE as a common problem with this vaccine.

Dr. Malone and Joe end the science-heavy portion of the podcast with a discussion around the difficulty of getting access to early treatments for COVID, specifically the monoclonal antibodies. Everything I am about to say is my own opinion, not my employer’s, thank you for understanding and this is a section where you may be better off listening to it directly. Dr. Malone and Joe are complimentary of the effectiveness of these treatments. Joe asks if they are ineffective against omicron; Dr. Malone states they are “less effective” based on “in vitro assessments of virus neutralization.”

Dr. Malone goes on to argue, likely correctly, that most of the hospitalizations right now are from delta, which is still transmitting in the US. Omicron may be growing in responsibility for more cases, but Dr. Malone correctly praises the South Africans and their early, well collected data that is holding up showing omicron is less severe than previous variants.

Joe and Dr. Malone discuss the wisdom, or lack thereof, of reducing access to treatments that may work on the more severe variants, especially as they are still circulating, just because omicron case numbers are climbing. Joe asks Dr. Malone how they can tell what variant has infected a particular patient.

I am not thrilled with Dr. Malone’s reply here, which mostly criticizes the model CDC uses to project which variants are most active.

The better answer is that we can sequence the full genome of the virus in the positive COVID test (from the same tube), and that is what gives us the variant. Health departments do this sequencing on a random and representative sample to determine what variant is spreading. However, it takes several days to a week to get this result. So the better answer to Joe is sequencing is how we do it, but it’s way too slow clinically to direct therapy towards a particular variant. You have a fairly short window from symptoms to get the antibodies or the new pills on board, or even your choice of ivermectin/HCQ if you are in a country that is using those for COVID. What the representative sample of sequences of positives reported to the health department means in practice is that we have solid statistical data on last week’s most common variant, and CDC models a projection for what this week’s variant spread is likely to be (the accuracy of this latter part is what Dr. Malone is criticizing) based on changes seen on that sequencing from prior weeks.

I will admit to being a little boggled myself over the availability and ease of accessing some of the early treatments. One anecdote from a high risk patient recently positive for COVID that came to me was that it took a lot of working the phone to find an infusion center that had monoclonal antibodies available (no one had the pills, or they were being restricted for the most high risk of patients). Positive late in the week before one of the recent holidays, the patient had to wait the entire weekend for an appointment on Monday, because the infusion center for COVID monoclonals was inexplicably (to me anyways) running only Monday through Friday and was off on holidays. If the goal is to minimize the number of hospital beds taken, and you have early treatments that are shown to reduce the need for hospitalization in high risk patients, in an on going pandemic, I do not understand why the early treatment centers are not running 24/7 or damn close to. Worse, this particular infusion center was still catching up on a backlog of patients whose time from symptoms may mean they were not quite acute COVID anymore, when those therapies may be less effective.

That covers most of the COVID specific content. The last 20-30 minutes then move from Joe and Dr. Malone discussing possible explanations for the relatively poor emphasis of early treatment. This portion of the podcast has caught a lot of headline attention, which is a shame, because there are some valid (and less valid) scientific points raised by Dr. Malone in the preceding hours of discussion. The crux is that Dr. Malone is a little quicker to ascribe to malice that which is best explained by stupidity than I am. As he states, “your only two explanations are they are just incompetent and that dumb, or there is a purpose to it.” What got the headlines is that the purpose he proposes is called “mass formation psychosis”, which I will not get into. You can listen to that part of the podcast.

More relevant parts he brings up BEFORE raising mass formation psychosis are “bonfire of the credibilities points” we have raised, and what some of the consequences of them will be. For example, he postulates, quite correctly I believe, that the horrible politicization of vaccination will have lasting public health consequences. He mostly criticized FDA’s decision to move fast on the vaccines (inappropriately, and he alleges, unethically), and believes the questions in a portion of the public’s mind towards those decisions and the politicization of vaccines will have turned millions of people who were NOT anti-vax before into people more likely to be anti-vax in general going forward. Including the ones with a proven safety and effectiveness record over decades. He also laments that medicine in general is being “destroyed” by this, with the reputation of doctors and the healthcare system writ large in tatters by association with these “inexplicable” decisions of the political health authorities, like CDC, NIH, and FDA.

So you may find some interest there, and again, you are better off listening to the “mass formation psychosis” discussion and determine for yourself how applicable, or not, it may be.

–One of the other points raised by Dr. Malone and Joe is the fear and schismogenesis being promoted through the incentives of social media and major news organizations. We have discussed that ad nauseum. Well, this podcast resurrected previous reports that governments from the UK to Canada (and undoubtedly beyond) made a concerted effort to deliberately ratchet the fear in messaging about coronavirus, even very early in the pandemic. In the UK reports specifically (write up is here), the government was concerned that individual citizens did not believe the threat to be personal enough to comply with lockdowns and other public health measures. So they deliberately ratcheted the fear inducing elements of reports. And continued to do so, even as some of those doing it felt it was “totalitarian” and an abuse of power per that linked report.

Remember: Why am I reading this? Why am I reading this now? What does this make me feel? Why does someone want me to feel this way?

Regardless, I am not surprised by reports that there were deliberate propaganda efforts throughout. Bernays wrote “Propaganda” (coined the phrase in fact) forever ago, and his disciples have used it ever since. It’s the nudges and emotional manipulation I have spoken of, from news, from government announcements, from social media. All of the venues for this kind of effort to reach, and persuade, and direct the opinions and beliefs of the many.

Bernays was pretty elitist, as are some of his followers, and truly believes that it is the right and duty of a small cadre of those who know how to manipulate the public opinion to do so and guide humanity to their expertly derived vision of society. They do this by restricting the focus to selected topics, and making sure nothing else gets oxygen in the public discussion. Then they further restrict the range of opinions on the selected topics. Schismogenesis is encouraged, because once you attach a belief or opinion or action to your identity, and your tribe, your paleo brain will fight to defend it. Even if it does not make objective sense. Finally, they make one opinion obviously “correct,” and this “resolution” of the tension pushes society where they want to go. Disturbingly, Bernays was pretty effective at this back in the day, and so this morally questionable and likely ultimately unwise playbook has perpetuated.

The problem is obvious. That small group of special people directing public discourse may NOT have the right solution, and could be steering everyone to a cliff. Absolute power corrupts absolutely, and if you have absolute power over propaganda, and human decision making as I argued before, you have a more potent weapon than the atomic bomb. No individual or small group can possibly be trusted with that power, because they will at some point become corrupted by it.

Bernays view of benevolent philosopher kings and queens directing the poor public, still stuck in Plato’s cave, to leave its chains for a brighter future, has a major moral failing as well. This approach, by definition, silences minority opinion that is an out group to this inner circle–even, sometimes especially, if that out group is being treated unjustly in pursuit of the small group defined “greater good.” The out group will then be silenced or trampled, with the ends of the greater good justifying this means of manipulation and censorship.

Worse, there is the challenge that this very much is a group of people in this world who read Bernays “Propaganda,” learn of the possibility and uses of this power and rejoice–because they believe themselves to be in that small group benevolently guiding humanity. Some of them might even really be in that small group. Other just believe themselves to be, or at least aligned with what they perceive to be its goals. Again, these ones who have attached to the beliefs emanating from the small group, who have now made it identity to them personally, these latter are the ones who have been most successfully co-opted by propaganda. They will defend the members of the small group voraciously, hoping to prove their worthiness of election to that elite or simply because they are now true believers, whose identity is tied up in the goals pushed by the small group. Even if the -actions- (a better indication of -real- belief) of the small group members do not align with the words and emotions used to rally public opinion.

If the kind of person who truly believes they are special, and specially chosen to guide humanity towards a goal only they can see, with skills only they have, and thus -deserve- that power, its privileges and exceptions to their own rules for others, gets into that small group, woe unto the world. For as Tyrion said, “It is easy to confuse the way things are with the way they ought to be, especially when the way things are has worked out so well for you.”

Given enough time, you will accidentally get a critical mass of people in that small group who are the kind of person that lacks the wisdom and introspection to ask the most important question demanded of that small group. The question that if Bernays cadre of benevolent cool kids, directing the course of public opinion to the promised land has to ask constantly to wisely and morally direct society this way:

<whispers>  What if we are wrong?

Because odds are good you will be.  Paleo brains and emotions, medieval institutions, Godlike technology.  That’s a challenging combination.  Now hand that godlike technology and insufficient institutions to a group of people who have convinced themselves they have the wisdom, knowledge and skill to run it, and further, it is their moral right and duty to run it, and to their specific goals, and watch what happens.

Spoiler alert—it’s what always happens when they believe they have the wisdom of a God, to determine right and wrong in their own judgment. Sex, money and power, in some combination, so loved by the paleo brain, eventually win and corrupt the entire edifice until it all collapses.

Just like the tower of Babel.

Whoever you pick for that small group, whoever that is, me, you, some ultracredentialed Tony Stark-like super genius, still has paleo brains and emotions too, after all. No matter how many Roman emperors and ancient kings declared themselves literally gods among men, they were all wrong, and only Shelley’s “Ozymandias” stands today in testimony to them.

–Or to paraphrase George Carlin, Bernays’ vision of the world, which the government manipulations of fear to get greater COVID measure compliance is in practice, is a big club for such a small number of people–and you ain’t in it.

–One final thought here. You will be tempted to believe that it is not you. That you have not succumbed to propaganda. That your beliefs have never been influenced by it. You will read what I have written in the paragraphs above, certain it convicts others, especially those whom you disagree with politically. Especially in the modern moment.

After all, who watches any of the variations of Dickens’ “A Christmas Carol” over these past holidays and thinks to themselves, “Man, -I- am kind of like Scrooge!”? We watch instead as Scrooge, this other guy, confronts the vice of greed that has corrupted his whole life, but at least get a redemption payoff at the end.

When really, if we are honest with ourselves, our difference is by degree, and which particular angel of a lesser nature has a hold on us. It may not be greed. You have at least 6 others to choose from.

Jacob Marley has come to warn us all. How often do we recognize that though?

So recognizing that it has happened, that it has happened to you too, and that no one, even you, can be trusted to be one of Bernays’ elite propagandist, the quiet cool kid puppet masters guiding society, without serious risk that your own all too human limitations may easily lead to disaster for untold many, is a start.

–I’m going to be honest though. In our current world, I struggle to find a plan B that is realistic given the incentives of what appear to be the main players.

–Maybe we all just need Jesus. ; )

–If there is any excuse for Bernays view it is that in a world awash with information, and so connected to every corner of the globe at once, with personalized content at your fingertips, something must focus attention on the important. Who decides, or the ends, are an issue as we discussed above. But the means can be a problem too. What if, in that world awash with information and distraction, Bernays’ acolytes need to elevate everything to “SUPER CRISIS APOCALYPSE” all the time just to get -any- kind of traction in the public consciousness? That might work for awhile to achieve their ends–but at the risk of failure due to diminishing returns, requiring ever more extreme stimulus, since we are constantly bombarded by new terrors every week, then every day, then every hour. Until news of the COVID zombie doom army riding a planet killer asteroid towards us eventually no longer registers as “wolf!” since Bernays’ boys have cried it once too many times. Maybe this is why we turn societally to the inane, to distract us from topics ratcheted to 11 just to try to capture any sliver of attention to them anymore? Eventually, we lose the ability to recognize real and important threats, and that is how the “Don’t Look Up” Netflix movie scenario (and a lot of pandemic response, frankly) happens, and society is NOT mobilized properly and in time to counter a real threat.

Maybe Bernays acolytes have been too many and too successful in the past, and his experiment in benevolent direction of society by elite propagandists fails not because they are corrupt, but because they can no longer capture the public’s attention?

–Semi-related, got sent this story that broke in the news media over the weekend, about the high rate of clinical false positives in prenatal genetic testing for extremely rare genetic disorders. An example of the coverage can be found here.

This is semi-related to COVID because it is entirely predictable, and related to the flaw in the “just test everyone with like a national COVID testing day using kits you send to everyone! We can quarantine all the positives, end the pandemic, high five and then have a beer.” We covered that here, and it’s worth reviewing there.

The problem is that the test can be highly analytically accurate (99.99% sensitive and specific, like a lot of genetic testing is, approximately to identify the mutation analytically). But if the disease is only present 0.0001% of the time, you will call “positive” many more cases with the test then actually have the disease.

Without re-hashing the math (again, go to the link above where we worked an example of this), the key is that if the incidence of the disease is more decimal places to the right of your assay’s sensitivity and specificity, you will have some false positives for every true positive (actual case of the rare disease) than you detect.

So as this relates to genetic testing, those blood screens for mutation should be getting used to steer any of the positives to a more invasive, but confirmatory test. As the Yahoo article linked at the beginning of this section details, that’s not always made clear in the information given about these tests, and not even the ordering healthcare provider always understands this. The math that is critical to know and understand was, no joke, only part of a 1 hour class in otherwise semester long class in epidemiology in medical school, and maybe a couple review questions on the licensure exams. It’s very easy to look at the analytical sensitivity and specificity numbers of 99.99% on the brochure or the pathology report and mistake them for the clinical positive predictive value (chance that a positive result on the test actually has the disease and is NOT false positive). The positive predictive value is what matters, and it depends critically on how common the disease is in the tested population.

All of my fellow physicians should keep that in mind, because it impacts ANY test for an uncommon or rare disease, or even a test you order knowing the patient has a low chance of actually having the disease beforehand.

For my own part, when my wife was pregnant with our kids, we declined these tests. Mostly because they would not have changed what we would have done, especially regarding termination. But also because I know the method, the tests, and what the likelihood of these was going to be. And declined.

Again, the golden rule of lab testing–don’t order a test if the result will not change what you do.

–Back to COVID briefly.

India has refused to issue emergency use authorization (as has the UK so far) for the Merck pill, based on concerns for mutagenicity, impacting pregnancy (Merck agrees with that one) and possible long term cancer risk. I’m just reporting the news on that–thank you for your understanding.

And the CDC and Fauci cannot get on the same page about “fully vaccinated.” Your state health department may have its own as well (Indiana does, for example). As of Thursday, CDC was considered “full vaccination” to be two vaccine doses, and “up to date” to include a booster at the appropriate time. They also shortened the interval between the two Pfizer vaccine doses–you can get them a little closer together now.

–I don’t know why, but for some reason I was thinking back to those years when “The Walking Dead” was at peak popularity, and all the headlines about how, as a planning exercise, the US government mocked up a zombie apocalypse hitting US shores. Partly, this was for how to deal with foreign invasion, but also because “the same preparations will help during a hurricane, pandemic [emphasis mine], earthquake or terrorist attack,” according to one of the articles describing this planning exercise still available on the internet’s memory.

Oh, the laughs we had then.

On the other hand, if this (gestures at 2020-2021) was the ideas and plan the government took from its “out of the box” planning scenario about the zombies…

…I, speaking purely as a concerned taxpayer, have some questions about the lessons the government believed it learned from that…

–And guys…we’re like two years into a global pandemic. We’ve seen the response thus far. You can come clean now.

Socioeconomic:

–To shorten this, only going to mention a few items.

1. China has reportedly instituted stricter internet controls on Xi’an, which has been locked down for several weeks now, and there are reports of civil unrest in the city as citizens are running out of food and finding difficult to get more with the current restrictions. More ominously for the rest of the globe, more new cases were discovered in Ningbo, prompting additional restrictions there, and activity is slowing at the port. As a reminder, Ningbo is the busiest port in the world by tonnage. Youzhou, a city 1.1 million, has had its transport system shut down and only essential food stores are allowed to be open as new cases were found there as well. The Winter Olympics are set to begin in China on February 4th.
2. In a possibly related story, Mercedes issued a recall for 800,000 cars due to the risk of the car catching on fire. Which is pretty serious. But in one of the best examples yet of the “missing widget” that supply chain bottlenecks, energy price and availability fluctuations, and various lockdowns worldwide over the past two years have caused, Mercedes does not have the part available to fix the problem. Instead, they have advised owners to drive the affected models “in a particularly prudent manner and usage reduced to the bare minimum.” They have no guidance for when they will get the part in to start fixing the affected cars. This impacts certain models powered exclusively by a diesel engine, and diesel Mercedes in these models are not available in the US (in case any readers own a Benz).
3. Kazakhstan, which has been wracked by protests against the government, causing it to hit the off switch on its internet, but not before calling for Russian and allied troops to quell riots that have burned government buildings. All because to maintain actual supply of gas, they had to lift price controls and sell the gas at cost as the government was having difficulty maintaining the spread between where it bought energy and where energy was selling at loss so the inflation did not slaughter its common citizen. They have ordered those price controls reimposed in a failed effort to pacify the riots, which followed energy prices doubling or tripling overnight this past weekend.

Deus impeditio esuritori nullus.

–Energy, its price and its supply, is something you should watch closely. It’s the next big threat to global supply chains this year.

–Finally, thank you to an astute reader who caught the real story in the following article.

Astute, because, as you have no doubt guessed, the true situation is much more dire.

18 were injured by a rampaging squirrel in Buckley, Wales shortly before New Years. What the article fails to mention is the true origin of the squirrel and exact circumstances, and how this is a significant escalation on multiple levels.

For some time now, unreported by the press, there have been small parties of squirrels and chipmunks conducting lightning raids, similar to this. The parties are often small, in and out raiders, using overwhelming violence of action or speed, surprise and guile to strike quickly and obtain the valuables and captives they seek. The raids actually began some few years ago, with the sack of the island of Lindisfarne in Northeast England. Seen as an odd, even adorable nuisance, the lack of organized resistance to their raids, and the rich bounties of baubles, nuts and captives available only brought forth more, and more frequent, attacks. For the past several summers now, coastal England from near Scotland down to the entire southern coast have been plagued by mysterious ships of aggressive rodents, invisible just off the coasts until they raise their terrible red sails to charge for the shore for vicious hit and run villainy.

Too often have the beleaguered citizens of England heard the terrible cry of these so-called Norsesquirrels before chaos and savagery, attacking their homes, their persons, their belongings has rained down as if by sudden divine punishment.

But as I mentioned, the situation is now worse for several reasons. First, this attack has happened in Wales, suggesting the raiders are extending their operations around the island, and soon the entire United Kingdom may be at risk. There are rumors already of permanent bases established by squirrels and chipmunks in the Hebrides and Orkney islands. This may explain how they have found the courage to risk sailing the North Sea in winter, instead of the usual summer “raiding season.” Secondly is the information they were able to glean from the captured squirrel in the article, which has, until now, been a deep state secret to keep the British population calm and carrying on…

It appears that the dread “Sons of Dave”, Alvin Davesson, Simon Davesson (called “the Ironside”) and Theodore the Boneless, have raised a mighty army of bloodthirsty, berserker squirrels and chipmunks. Already, one can almost hear the war drums and the harsh pagan chants of the cults of Thor and Odin–led by Alvin, Simon and Theodore. The echoes on the nights where only the eerie glow of the aurora borealis gives light, which ride the chill north winds, all whisper “SKOL!” once more.

Yes, a Great Heathen Army sails the North Seas again, more terrifying even than the ones which first haunted Albion these hundreds of years ago.

Forget what they told Oprah. The threat of the Sons of Dave and their army is so great that Harry and Megan departed not to start a new life away from royal pressures, but to far distant shores–across an ocean, then a continent–to ensure the continuity of the crown should the worst happen.

The Queen of England, like her predecessor Alfred the Great so long ago, has raised the fyrds. Now, it is a waiting game, for they know not when the dread raven banners of the Sons of Dave will sail for the final confrontation, or where they will land.

Only that they will come.

But your chances of catching COVID this week are equivalent to the chances that the sons and daughters of old Northumbria, of Mercia and of Wessex — of England — now united with the sons and daughters of Gwynedd, Powys and Gwent, of Connachta and Ui Neill, of ancient Alba, will be ready.

<Paladin>